1. Field of the Invention
The present invention relates to PRLTS proteins, DNAs encoding the proteins and methods of discriminating tumor cells in which use is made of the DNAs. The present invention is usefully applied in the fields of medical science and pharmaceuticals.
2. Description of the Related Art
There has long been a conception that mutations in cellular proteins play an important role in carcinogenesis. The progress of genetic engineering achieved in recent years has made it possible to analyze the amplification of the DNA encoding a specified protein and gene mutations in tumor cells, thereby rapidly advancing cancer research.
The analysis and identification of genes (oncogenes) encoding proteins believed as participating in the malignant alteration of cells and the abnormal proliferation of tumor cells have been promoted, so that the identification of such genes number in the tens. On the other hand, counteracting genes (tumor suppressor genes) are highlighted in recent years. Tumor suppressor genes hitherto discovered include the Rb gene capable of suppressing retinoblastoma Friend, S. H., et al., Proc. Natl. Acad. Sci. USA., 84, 9095 (1987)!, the p53 gene capable of suppressing colorectal cancer Lane, D. P., et al., Nature, 278, 261 (1979)!, the APC gene capable of suppressing colorectal cancer Kenneth, W. K., et al., Science, 253, 661 (1991)! and the WTI gene capable of suppressing Wilms' tumor Call, K. M., et al., Cell, 60, 509 (1990)!. With respect to the p53 gene, cases are known in which germ-line mutations in the gene are inherited "Li-Fraumeni syndrome" (Makin, D., et al., Science, 250, 1233 (1990); and Srivastava, S., et al., Nature, 348, 747 (1990))!. It is gradually becoming apparent that defects in not only a single gene but also in multiple genes participate in the progression of the malignant phenotype of cancer, and it is believed that there will be further discovered a large number of unidentified oncogenes and tumor suppressor genes. Their discovery and elucidation are anticipated by not only research and clinical experts but also people worldwide.
It is estimated that there are about 4500 genes on the human chromosome 8, and to now the presence of genes causative of genetic diseases such as Langer-Gideorn syndrome, Werner syndrome and pigmentous retinitis is suggested on this chromosome. The present inventors and other researchers reported Emi, M., et al., Cancer Res., 52, 5368-5372 (1992)! that on the short arm of the human chromosome 8 there is a site frequently deleted in various tumors such as lung cancer Ohata, H., et al., Genes Chromosomes & Cancer, 7, 85-88 (1993)!, hepatocellular carcinoma Emi, M., et al., Genes Chromosomes & Cancer, 7, 152-157 (1993)!, colorectal cancer Fujiwara, Y., et al., Cancer Res., 53, 1172-1174 (1993)!, prostatic cancer Bererheim, U., et al., Genes Chromosomes & Cancer, 3, 215-220 (1991)! and bladder cancer (Knowles, M. A., et al, Oncogene, 8, 1357-1364 (1993)! and that, hence, the presence of an important tumor suppressor gene capable of participating in various cancers is foreseen in the above deletion site.
Therefore, isolation of the causative gene present in the above site and identification of a protein corresponding thereto are now themes of great concern of not only worldwide doctors and researchers but also the general public, whose attainment is highly anticipated.